The modulation of neutrophil (PMN) function has been studied by assessing chemoattractant receptors, cytoskeleton function, chemotaxis, degranulation and oxidative metabolism in normal and abnormal cells. The data indicate there is an intracellular pool of receptors for the chemoattractant fmet-leu-phe with the density of specific granules that are mobilized to the plasma membrane with cell activation. These data, together with studies in neutrophil cytoplasts, support the concept that specific granules are a reservoir of receptors and show that receptor mobilization is independent from receptor affinity adaptation. In studies of factors regulating chemotaxis, high extracellular potassium, was shown to activate PMN capping of lectin receptors and induce shape changes, similar to chemoattractants. Since potassium would be expected to be increased at inflammatory foci, where there are dead or dying cells, the data suggest potassium may exert an important modulatory role on the inflammatory response. Abnormal "turn-off" of acute inflammatory reactions was seen in chronic granulomatous disease (CGD) with persistence of PMN late in experimental inflammation. This indicates different biochemical lesions can be manifest as phenotypic disease. Other clinical studies revealed that incubation of monocytes from patients with the Hyperimmunoglobulin E-Recurrent infection (Job's) syndrome with S. aureus causes release of an inhibitor of PMN chemotaxis. In addition, sera and saliva from patients with Job's syndrome was shown to be deficient in antistaphylococcol IgA. New approaches for pharmacologic manipulation of PMN function were explored. Auranofin, an oral gold compound used to treat rheumatoid arthritis, induced high affinity states of the PMN receptor for fmet-leu-phe and perferenitially inhibited oxidative metabolism and lysozyme secretion. The data suggest pharmacologic control of PMN chemoattractant receptors may provide a tool for selective manipulation of functions activated by these receptors.